[An experimental study on choroidal neovascularization inhibited by adenoviral vectored pigment epithelium-derived factor].
OBJECTIVE
To study the effect of adenoviral vectored pigment epithelium-derived factor (AdPEDF) gene transfer on established neovascularization in a rat model of choroidal neovascularization (CNV).


METHODS
It was a experimental study. Sixty-eight female BN rats (136 eyes) with 6 to 8 weeks were used in this study. After the CNV model founded, 68 rats were divided into 5 groups with simple random sampling method. Four of them (8 eyes) were randomly selected as normal control group and 64 rats (128 eyes) were as experimental group. The experimental group included intravitreal injection with AdPEDF 1 microliter (group A), intravitreal injection with control vector (AdNull) 1 microliter (group B), periocular injection with AdPEDF 1 microliter (group C), and periocular injection with AdNull 1 microliter (group D). Histopathology, TUNEL staining, fundus fluorescein angiography (FFA), and thickness of CNV were tested 3, 7, 14, and 28 days after injection.


RESULTS
(1) The leakages appeared decrease after treatment in group A (54.7%) and C (56.3%) (t = 2.75, t = 3.15; P < 0.01). (2) CNV decreased in group A (57.3%) and C (57.8%) 7 days after injection, and kept fibrovascular proliferation in group B and D. (3) The thickness of CNV in group A [(44.51 +/- 0. 53) micrometers] and C [(44.37 +/- 0.48) micrometers] was significantly less than that in normal control group [(46.35 +/- 0.93) micrometers] after the treatment (F = 7.57, 8.85; P < 0.01), and it diminished with the time prolong (F = 4.31, 5.25; P < 0.05). The thickness of CNV in group A [(46.35 +/- 0.62) micrometers] was greater than that in group C [(44.90 +/- 0.44) micrometers] 3 days after treatment (F = 3.55, P < 0.05), and it was less in group A than that in group C 14 and 28 days after treatment (F = 6.54, P < 0.01; F = 4.41, P < 0.05). (4) There were positive TUNEL stainings in choroidal neovascular endothelium in group A and C. (5) Postoperative complication included cataract (5 eyes) after intravitreal injection.


CONCLUSIONS
AdPEDF is effective in inhibiting CNV in an animal model. The effect appears 7 days after treatment, reaches the peak on day 14, and keeps stable on day 28. The inhibition effect on CNV appears slowly in eyes with intravitreal injection than that with periocular injection, and it is stronger in eyes with intravitreal injection.
Yan
Hua
H
Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin 300052, China. phuayan2000@yahoo.com
Wang
Ying
Y
Cui
Jing
J
Yu
Yan-ping
YP
D000256:Adenoviridae / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D020256:Choroidal Neovascularization / Q000628:therapy*; D005136:Eye Proteins / Q000627:therapeutic use*; D005260:Female; D015316:Genetic Therapy; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D051381:Rats; D011914:Rats, Inbred BN; D015843:Serpins / Q000627:therapeutic use*; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor